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Article Dans Une Revue eLife Année : 2017

Optical control of pain in vivo with a photoactive mGlu5 receptor negative allosteric modulator

Serena Notartomaso
Pamela Scarselli
Paola Di Pietro
Giuseppe Battaglia
Xavier Rovira
Jean-Philippe Pin
Víctor Fernández-Dueñas
Cyril Goudet
Amadeu Llebaria
  • Fonction : Auteur
  • PersonId : 1107464
Francisco Ciruela
  • Fonction : Auteur
  • PersonId : 1104347

Résumé

Light-operated drugs constitute a major target in drug discovery, since they may provide spatiotemporal resolution for the treatment of complex diseases (i.e. chronic pain). JF-NP-26 is an inactive photocaged derivative of the metabotropic glutamate type 5 (mGlu 5) receptor negative allosteric modulator raseglurant. Violet light illumination of JF-NP-26 induces a photochemical reaction prompting the active-drug's release, which effectively controls mGlu 5 receptor activity both in ectopic expressing systems and in striatal primary neurons. Systemic administration in mice followed by local light-emitting diode (LED)-based illumination, either of the thalamus or the peripheral tissues, induced JF-NP-26-mediated light-dependent analgesia both in neuropathic and in acute/tonic inflammatory pain models. These data offer the first example of optical control of analgesia in vivo using a photocaged mGlu 5 receptor negative allosteric modulator. This approach shows potential for precisely targeting, in time and space, endogenous receptors, which may allow a better management of difficult-to-treat disorders.
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Dates et versions

hal-03549950 , version 1 (31-01-2022)

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Joan Font, Marc López-Cano, Serena Notartomaso, Pamela Scarselli, Paola Di Pietro, et al.. Optical control of pain in vivo with a photoactive mGlu5 receptor negative allosteric modulator. eLife, 2017, 6, ⟨10.7554/elife.23545.001⟩. ⟨hal-03549950⟩
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